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JAMA Network Open | January 4, 2022 | Volume: 5 | Issue: 1 | Pages: e2142046
Association of Convalescent Plasma Therapy With Survival in Patients With Hematologic Cancers and COVID-19
Shah, Pankil , Rubinstein, Samuel M. , Joyner, Michael J. , Choueiri, Toni K. , Flora, Daniel , Gulati, Anthony P., Koshkin, Vadim S. , Papadopoulos, Esperanza B. , Robilotti, Elizabeth , Su, Christopher , Wulff‐Burchfield, Elizabeth , Xie, Zhuoer , Yu, Peter Paul , Mishra, Sanjay , Senefeld, Jonathon W. , Shah, Dimpy P. , Verma, Amit , Gartrell, Benjamin A. , Ohri, Nitin , Butt, Omar H. , Campian, Jian , Fiala, Mark A. , Monahan, Ryan, Bohachek, Pamela, Mundt, Daniel , Streckfuss, Mitrianna, Tadesse, Eyob, Lammers, Philip E. , Revankar, Sanjay G. , Khan, Hina, Prete, Salvatore A. 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JAMA Oncology | August 19, 2021 | Volume: 7 | Issue: 8 | Pages: 1167
Circulating Cell-Free DNA as Biomarker of Taxane Resistance in Metastatic Castration-Resistant Prostate Cancer
Francini, Edoardo , Ou, Fang‐Shu , Wolfe, Eric, O’Connor, Edward , Gydush, Gregory, Kelleher, Kaitlin M. , Bhatt, Rupal S. , Balk, Steven P. , Sweeney, Christopher J. , Adalsteinsson, Viktor A. , Taplin, Mary‐Ellen , Choudhury, Atish D. , Wolfe, Eric G, Balk, Steven , Choudhury, Atish D , Ou, Fang-Shu , Sweeney, Christopher , Rhoades, Justin , Ha, Gavin
Cancers | August 12, 2021 | Volume: 13 | Issue: 16 | Pages: 4055
There are no biomarkers predictive of resistance to docetaxel or cabazitaxel validated for patients with metastatic castration-resistant prostate cancer (mCRPC). We assessed the association between ABCB1 amplification and primary resistance to docetaxel or cabazitaxel for patients with mCRPC, using circulating cell-free DNA (cfDNA). Patients with ≥1 plasma sample drawn within 12 months before starting docetaxel (cohort A) or cabazitaxel (cohort B) for mCRPC were identified from the Dana–Farber Cancer Institute IRB approved database. Sparse whole genome sequencing was performed on the selected cfDNA samples and tumor fractions were estimated using the computational tool ichorCNA. We evaluated the association between ABCB1 amplification or other copy number alterations and primary resistance to docetaxel or cabazitaxel. Of the selected 176 patients, 45 samples in cohort A and 21 samples in cohort B had sufficient tumor content. No significant association was found between ABCB1 amplification and primary resistance to docetaxel (p = 0.58; odds ratio (OR) = 1.49) or cabazitaxel (p = 0.97; OR = 1.06). No significant association was found between exploratory biomarkers and primary resistance to docetaxel or cabazitaxel. In this study, ABCB1 amplification did not predict primary resistance to docetaxel or cabazitaxel for mCRPC. Future studies including ABCB1 amplification in a suite of putative biomarkers and a larger cohort may aid in drawing definitive conclusions.
Circulating-free DNA (cfDNA) as biomarker of taxane resistance in metastatic castration-resistant prostate cancer (mCRPC).
Francini, Edoardo , Wolfe, Eric, O’Connor, Edward , Gregory, Gydush, Kelleher, Kaitlin M. , Bhatt, Rupal S. , Adalsteinsson, Viktor A. , Taplin, Mary‐Ellen , Ou, Fang‐Shu , Rhoades, Justin , Ha, Gavin , Balk, Steven P. , Sweeney, Christopher J. , Choudhury, Atish D.
Journal of Clinical Oncology | February 19, 2020 | Volume: 38 | Issue: 6_suppl | Pages: 174-174
10.1200/jco.2020.38.6_suppl.174
174 Background: Docetaxel (D) and cabazitaxel (C) are standard chemotherapies for mCRPC. A reliable biomarker predictive of resistance to D or C is yet to be identified. We aimed to assess the association between genetic amplification of the multidrug resistance transporter ABCB1 (ABCB1 amp) and primary resistance (RES) to D or C for mCRPC, using cfDNA. Methods: A cohort (A) of 136 patients (pts) with at least 1 plasma sample drawn and stored within 1 year prior to starting D for mCRPC (2002-2014) and a cohort (B) of 42 pts with at least 1 plasma sample from within 1 year prior to starting C for mCRPC (2010-2016) were identified from the Dana-Farber Cancer Institute IRB approved database. Whole genome sequencing (WGS) at 0.1x coverage, termed ultra-low pass WGS (ULP-WGS), was performed on cfDNA extracted from the selected samples (1000μL/subject) and sequencing data were analyzed using a tool called ichorCNA to identify cases with sufficient tumor DNA content (>7%) for accurate detection of copy number alterations (CNAs) including ABCB1 amp. Primary objective was the association between ABCB1 amp and RES to D or C. RES was defined as lack of response (no PSA50 decline or radiologic response per RECIST criteria 1.1, within 4 months from treatment start). Odds ratio (OR) was used to compare odds of RES to D or C for pts with ABCB1 amp and P-values were calculated by Fisher’s exact test. Results: Of the selected 178 pts, 66 had tumor fraction >7%: 45 pts in cohort A and 21 in cohort B. No significant association was noted between ABCB1 amp and RES to D (P=0.7123; OR=1.600) or C (P=1.000; OR=1.0606). RES was observed in 26 pts (57.8%) of cohort A and 18 (85.7%) of cohort B. ABCB1 amp was found in 9 pts (20%; 95% CI, 9.6-34.6) in group A and 6 of them (66%) had RES to D. ABCB1 amp rate among D-resistant men was 23.1% (95% CI, 9.0-43.7). In group B, 2 pts (9.5%; 95% CI, 1.2-30.4) had ABCB1 amp and both of them had RES to C. ABCB1 rate among C-resistant pts was 11.1% (95% CI, 1.4-34.7). Conclusions: In this study, ABCB1 amp using cfDNA did not show statistically significant correlation with RES to D or C for pts with mCRPC. Future studies including ABCB1 amp in a suite of putative biomarkers and larger sample size may aid drawing definitive conclusions.